tbuckley/cabot-search huggingface dataset:
ASCEND: A randomised, double-blinded, phase II study of gemcitabine and nab‐paclitaxel with CEND‐1/LSTA1 or placebo in patients with untreated metastatic pancreatic ductal adenocarcinoma.
Authors: Andrew Peter Dean, Timothy Jay Price, Katrin Marie Sjoquist, Val Gebski, Jan Mumford, Fiona Day, Sonia Yip, Nathan Bradshaw, Christopher G. C. A. Jackson, Shamsudheen Padinharakam, Belinda Lee, Matthew E. Burge, Niall C. Tebbutt, Christopher B. Steer, Chris Lomma, Lyn Lam, Joanna Lee, Lorraine A. Chantrill, Marion Harris
Journal: Journal of Clinical Oncology (2023)

TPS4197 Background: LSTA1 is a novel cyclic peptide with high tumor vascular endothelium specificity that activates an endocytotic/exocytotic transport pathway on stroma and tumor. LSTA1 potentiates greater intratumoral access for co-administered or tethered anti-cancer agents, including small molecules, antibodies, and nanoparticles, leading to increased anti-neoplastic activity. Preclinical studies in solid tumor models have shown co-administrating LSTA1 is effective in augmenting the delivery and activity of multiple anti-cancer agents. LSTA1 has been evaluated in 31 patients in a Phase I study in metastatic pancreatic ductal adenocarcinoma (mPDAC) demonstrating an objective response in 59% of patients, a 79% disease control rate at 16 weeks with a median progression free survival (PFS) of ~9.9 months. No dose limiting toxicities were observed. The ASCEND study will determine whether LSTA1 when added to SOC chemotherapy is active and safe as first-line treatment of mPDAC, and whether an additional dose of LSTA1 administered approximately 4 hours after chemotherapy further improves anti-cancer activity. Methods: ASCEND is a randomized, double-blind, placebo-controlled phase II trial evaluating the safety and efficacy of LSTA1 3.2 mg/kg in combination with standard of care chemotherapy (nab-paclitaxel 125mg/m 2 and gemcitabine 1000mg/m 2 on days 1, 8, and 15, every 28 days) in patients with histologically proven, previously untreated mPDAC. A total of 155 subjects will be randomized 2:1 in favor of study intervention in two cohorts and stratified by age, ECOG status, presence of liver metastasis, and study site. Patients in cohort A receive single doses of LSTA1 or placebo, and for cohort B, two doses of LSTA1 or placebo spaced 4 hours apart. Tumour assessment occurs every 8-weeks from randomization until disease progression or commencement of a new anti-cancer therapy. The primary endpoint is PFS. Secondary endpoints include objective tumour response safety, overall survival, and patient reported outcomes. At 14 Feb 2023, 70 participants have been enrolled from Australian sites. Sites in Ireland and New Zealand are anticipated to open this year. Clinical trial information: NCT05042128 .
Disparities in screening, diagnosis, treatment, and survivorship care among urban and rural patients with colorectal cancer in the United States: A systematic review and meta-analysis.
Authors: Aryana Sepassi, Meng Li, Jason A. Zell, Alexandre Chan, Ila M Saunders, Dana B Mukamel
Journal: Journal of Clinical Oncology (2023)

e18558 Background: Older rural patients suffer from disproportionately higher rates of colorectal cancer (CRC) and mortality due to CRC compared to older urban patients. These disparities may be multifactorial including geographic barriers to care, lack of health insurance coverage, or lack of preventive health behaviors, among others. To further understand this burden of rural-urban CRC disparities along the cancer care continuum, we sought to evaluate and synthesize literature on screening, diagnosis, treatment, and survivorship care differences between urban and rural CRC patients. Methods: We performed a systematic literature review using PubMed and EMBASE in August 2022 using keywords related to screening, diagnosis, treatment, and survivorship care for CRC urban-rural patients for studies published in 2000 to 2022. A meta-analysis was performed for results related to screening using a random-effects model. Results: Of 836 studies collected, 46 met criteria for review, and 12 for a meta-analysis evaluating the effect of rurality on any reported CRC screening. The majority of studies evaluated disparities in screening (46%), followed by diagnosis (30%), treatment (20%), and survivorship care (4%). In general, studies indicated urban CRC patients as more likely to report age-appropriate screening, to receive early-stage diagnosis, and to receive timely and appropriate treatment compared to rural CRC patients. Only one study was found evaluating a difference in receipt of surveillance colonoscopy in urban/rural CRC survivors, with rural survivors as 2.28 times more likely to report nonadherence to surveillance screening (OR = 2.28, 95%CI:1.07-4.85). Meta-analysis results indicate that rural patients had 22% lower odds of reporting screening compared to urban patients prior to any diagnosis (pooled OR = 0.78, 95%CI:0.66-0.92, I 2 = 42.9%). Conclusions: Despite widespread support and effort to implement policy aimed toward reducing disparities of care, screening, diagnosis, and treatment gaps are still present between urban and rural CRC patients. Further research must be performed to evaluate the effects of these disparities on clinical outcomes in the rural CRC patient population.
Survey of carboplatin desensitization therapy: JCOG Gynecologic Cancer Study Group multicenter retrospective study.
Authors: Hiroaki Komatsu, Koji Matsumoto, Shin Nishio, Mitsunori Morita, Takayuki Nagasawa, Hiroshi Nishio, Jiro Suzuki, Mitsuya Ishikawa, Toyomi Satoh
Journal: Journal of Clinical Oncology (2023)

e17631 Background: The purpose of the present study was to investigate the real-world experience with carboplatin desensitization (CD) therapy in Japan, along with its safety, and establish a strategy to address carboplatin-induced hypersensitive reactions (HSRs). Methods: The present study included patients diagnosed with gynecologic cancer (ovarian, endometrial, or cervical cancer, i.e., OC, EC, and CC, respectively) who underwent CD therapy between 2016 and 2020 at Japan Clinical Oncology Group Gynecologic Cancer Study Group (JCOG-GCSG) participating centers. CD therapy was performed at each institution, and cases of implementation were registered in online case report forms. We examined patient information, treatment regimens, frequency and dose of carboplatin administration, administration rates, and CD practices. This study was approved by the Ethics Committee of the Tottori University. Results: Overall, 20 of 51 JCOG-GCSC-participating facilities performed CD therapy. The present study enrolled 136 patients (OC, 108; EC, 17; CC, 11). Of these, 37 (27.2%) patients had pre-existing allergies, and 29 (20.5%) exhibited prodromal symptoms at the time of treatment prior to the onset of HSRs. The most common symptoms were erythema and itching. At the onset of HSRs, erythema was the most common symptom, occurring in 93 (68.4%) patients, followed by itching in 72 (52.9%), reduced oxygen saturation in 43 (31.6%), and loss of consciousness in 3 (2.2%). The onset of HSRs was most common during treatment of the first recurrence (47%). The mean total carboplatin dose until the appearance of HSRs was 7331 (2620–18282) mg, and the mean number of doses was 14 (4–63). Six centers discontinued CD therapy owing to the appearance of breakthrough HSRs. CD therapy was completed in 75% of patients, with 25% (34/136) experiencing breakthrough HSRs. HSR-related mortality was not observed. The associated risk factors with HSR were not selected in the present study. Conclusions: Although patients who undergo CD therapy in Japan have a high probability of safely completing planned therapy, erythema and pruritus are important signs of breakthrough HSRs. Breakthrough HSRs were most frequent during the first cycle of desensitization. [Table: see text]
Prognostic factors for relapse in patients with clinical stage I testicular seminoma: A nationwide, population-based cohort study.
Authors: Thomas Wagner, Birgitte Grønkær Toft, Jakob Lauritsen, Mikkel Bandak, Ib Jarle Christensen, Birte Engvad, Michael Kreiberg Jessen, Mads Agerbaek, Lars Dysager, Josephine Rosenvilde, Daniel Berney, Gedske Daugaard
Journal: Journal of Clinical Oncology (2023)

5041 Background: Approximately 20% of patients with clinical stage I testicular seminoma will relapse after orchiectomy. No robust prognostic factors for relapse exist which challenges risk assessment and counselling for patients. Previous studies have been hampered by selection bias and variable pathology reporting that limit interpretation and generalization of results. We therefore assessed prognostic factors for relapse in a large unselected nationwide population-based setting with centralized pathology review. Methods: Patients with clinical stage I seminoma diagnosed in Denmark between 2013 and 2018 were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, microscopic slides from the orchiectomy specimens were retrieved and reviewed blinded to the clinical outcome. Clinical data were obtained from medical records with follow-up until July 2022. The association between prespecified clinical and histopathological prognostic factors and relapse were assessed by use of Cox regression analysis. Potential prognostic factors included age, pre-orchiectomy values of β-human chorionic gonadotropin (β-hCG) and lactate dehydrogenase (LDH), tumor size, tumor multifocality, tumor necrosis, lymphovascular invasion, pagetoid rete involvement, and invasion of rete testis, hilar soft tissue, epididymis, spermatic cord, tunica albuginea, and tunica vaginalis. Results: In total, 924 patients were included. During a median follow-up of 6.3 years, 148 (16%) patients relapsed. Invasion of the testicular hilum (rete testis and hilar soft tissue), lymphovascular invasion, and elevated pre-orchiectomy levels of β-hCG and LDH were independent predictors of relapse. The estimated 5-year risk of relapse ranged from 6% in patients with no risk factors, to 64% in patients with all four risk factors with tumor extension into the hilar soft tissue of the testicular hilum. After internal model validation, the model had an overall concordance statistic of 0.70. Conclusions: The provided prognostic factors allow a long-awaited opportunity to make more informed treatment decisions about post-orchiectomy management in patients with clinical stage I seminoma. These should replace current risk factors in guidelines and be used in future studies investigating risk-adapted follow-up and treatment strategies. [Table: see text]
Immune activation-related risk score: A new tool to predict prognosis and immunotherapy applicability in colorectal cancer.
Authors: Changbin Zhu, Wenqing Su, Yanhua Chen, Fei Gai, Jin Wang
Journal: Journal of Clinical Oncology (2023)

e15534 Background: In colorectal cancer (CRC), the therapeutic potential of immune checkpoint inhibitors (ICIs) is limited to the patients with mismatch repair deficient (dMMR)/high microsatellite instable (MSI-H) tumors, which accounts for less than 5% of CRC patients. While, patients with mismatch repair proficient (pMMR)/microsatellite stable (MSS) tumors represent the vast majority (≈ 95%), particularly those with similar inflammatory tumour microenvironment characteristics to dMMR/MSI-H patients are at risk of losing the opportunity to receive appropriate treatment. Thus, there is an urgent clinical need for biomarkers that can accurately predict prognosis of CRC patients, and assist in selection of patients who may benefit from immunotherapy. Methods: A public database, GEO (GSE39582, n = 502), was used as a training cohort to assess the characteristics associated with immune activation. Individuals with immune characteristics similar to dMMR/MSI-H were identified through GSVA and unsupervised clustering analysis, and defined as MSI-Like. Limma analysis identified MSI-Like immune activation characteristic, and immune activation-related prognostic models were developed by LASSO and COX regression. In addition, the applicability of immunotherapy for immune activation-related prognostic score was estimated in an external validation cohort (n = 96) from an Asian institution. Results: 113 differentially expressed genes between MSI-Like and non-MSI-Like pMMR/MSS samples were defined as immune activation- related characteristics of MSI-Like. After stepwise regression analysis, the characteristics were reduced to 6 key genes, and combined with their regression coefficients to construct a model. Overall survival was significantly shorter in high-risk [Immune Activation-related Risk Score (IARS) ≥ 0] group than in low-risk (IARS &lt; 0) group (p &lt; 0.0001). The area under the ROC curve (AUC) values at 1, 5 and 10 years were 0.683, 0.708 and 0.765, respectively. Furthermore, in multiple CRC data sets, the IARS can screen out the low-risk group with significantly better prognosis (p &lt; 0.05). Additionally, low-risk group showed more expression of immune activation-related genes compared to high-risk group. IARS did not shown significant correlations with clinically characteristic factors (e.g., gender, age, stage, etc.) or gene mutations (including TP53, KRAS and BRAF). Conclusions: For a subset of pMMR/MSS patients with immune activation characteristics similar to those of dMMR/MSI-H patients, an immune activation-related risk score model was constructed based on 6 genes associated with immune activation characteristics. This model can effectively predict the prognosis of patients and also help to assess the adaptability of patients to immunotherapy. These findings have the potential to provide new insights into the immunotherapy of patients with pMMR/MSS CRC.
Monitoring epithelial, epithelial-mesenchymal, and mesenchymal circulating tumor cells on papillary thyroid cancer following thyroidectomy: A prospective cohort study.
Authors: Eunju Park, Hyeong Won Yu, Seon Kyoung Lee, Ju Hyun Kong, Joseph Sunoo, Soon-Cheol Hong, June Young Choi
Journal: Journal of Clinical Oncology (2023)

6097 Background: Monitoring the effectiveness of cancer-removal surgery is challenging in most cases. Therefore, robust and non-invasive techniques have been developed, and liquid biopsy is an apparent method for that purpose. In this prospective cohort study, we examined whether one type of liquid biopsy, an enumeration of circulating tumor cells (CTCs), can monitor the effectiveness of thyroidectomy in patients with papillary thyroid cancer (PTC). Methods: From January 2021 to January 2022, we recruited 62 PTC patients who had operated on isthmectomy, lobectomy, and total thyroidectomy for this study at Seoul National University Bundang Hospital. The blood samples from the recruited patients were collected before surgery and two weeks and three months after the surgery for CTC detection. We collected peripheral blood samples by venipuncture from each patient in EDTA tubes and stored them at 4°C until isolation and characterization of CTCs (within 6 hours). Results: We found the CTCs in 87% (54/62) of PTC patients, with an average number of 8.0. This number significantly decreased after thyroidectomy, with an average of 5.3 and 4.3 post-operation of two weeks and three months, respectively. In the peripheral blood of PTC patients, the CTCs with epithelial-mesenchymal and mesenchymal phenotypes were significantly more frequent than the epithelial phenotype of CTCs. Furthermore, PTC patients with lymphatic invasion, lymph node metastasis, or BRAF V600E mutation showed significantly decreased CTC count after surgery. Conclusions: PTC patients had a significantly higher number of CTCs undergoing epithelial-mesenchymal transition and showed a significant decrease in CTC count after surgery. This indicates that liquid biopsy using CTC enumeration can satisfy the purpose of monitoring the effectiveness of cancer-removal surgery. Clinical trial information: KCT0008179.
Neoadjuvant chemoimmunotherapy for the treatment of locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: A single-arm phase 2 clinical trial.
Authors: Yanfeng Chen, Ankui Yang, Yan-Ping Mao
Journal: Journal of Clinical Oncology (2023)

6077 Background: Standard treatment for patients with locally advanced laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) is total laryngectomy, which seriously affects the quality of life. Neoadjuvant treatment with Nab-paclitaxel plus cisplatin(TP) has favorable efficacy with acceptable toxicity for laryngeal preservation in LHSCC. Programmed death 1 (PD-1) blockade plus chemotherapy has shown a survival benefit and recommended as the first-line treatment in recurrent or metastatic head and neck cancer, but the safety and activity in the combination of TP and PD-1 blockade in locally advanced LHSCC need investigation. Methods: In this single-center, single-arm, phase 2 trial, newly diagnosed pts with stage T3-4N0-3M0 laryngeal SCC or T2-4N0-3M0 hypopharyngeal SCC were recruited. Eligible patients received chemotherapy [Nab-paclitaxel 240 mg/m 2 plus cisplatin 75 mg/m 2 ] and toripalimab[240 mg, d1]every 3 weeks for 3 cycles. After induction treatment, patients achieving clinical partial response (cPR) or complete response (cCR) received definitive radiotherapy, while those with stable diseases(SD) and progression disease(PD) received surgery plus adjuvant radiotherapy. Toripalimab was given intravenously once every 3 weeks for up to 10 cycles, including 3 cycles before. The primary endpoint was the objective response rate (ORR) according to RECIST 1.1 by investigator assessment to neoadjuvant chemoimmunotherapy. The secondary endpoints included laryngectomy-free survival (LFS), disease failure-free survival (DFS)and overall survival OS at 2 years, quality of life (QOL) and toxic effects. Results: From October 2020 to May 2022，25 patients received neoadjuvant chemoimmunotherapy (median age 58 years; 23.9% men), 52% (13/25) and 48% (12/25) were hypopharyngeal and laryngeal squamous cell carcinoma. 80% (20/25) were clinical T3/4 and 64.0% (16/25) ≥N2. After neoadjuvant chemoimmunotherapy, 2 patients achieved CR, 21 achieved PR, with an ORR of 92%(23/25), 23 patients with CR/PR of the primary tumor received concurrent radiotherapy and immune maintenance therapy, 2 patients with SD/PD received laryngectomy. At a median follow-up of 17 months (range 8-27 months), 1-year DFS was 88.0% , 1-year OS was 96.0% , 1-year LPS was 92.0%, Respectively, only grade 1-2 adverse events occurred in 100% of patients, including loss of appetite (100%), anemia (92.0%), nausea (84.0%), vomiting (52.0%), hypothyroidism (16.0%), peripheral neuritis (20%), leukopenia (12.0%), rash (12.0%). Conclusions: Neoadjuvant treatment with TP plus toripalimab achieved impressive ORR and 1-year LPS rate with manageable toxicities in patients with LHSCC. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: ChiCTR2000033506 .
A multicenter, open-label, randomized phase II study evaluating adjuvant gemcitabine plus cisplatin (GC) and capecitabine with concurrent capecitabine radiotherapy (CAPE-RT) in patients with operated gallbladder adenocarcinoma (GBC): The GECCOR-GB trial.
Authors: Anant Ramaswamy, Vikas S. Ostwal, Reena Engineer, Manali Parulekar, Sarika Mandavkar, Nanda Aier, Prabhat Ghanshyam Bhargava, Sujay Srinivas, Shraddha Patkar, RAHUL KRISHNATRY, Shivakumar Gudi, Akhil Kapoor, Durgatosh Pandey, Swapnil Patel, Abhishek Shinghal, Alok Goel, Tapas Kumar Dora, Debashish Chaudhary, Suman Kumar Ankathi, Mahesh Goel
Journal: Journal of Clinical Oncology (2023)

4017 Background: Adjuvant gemcitabine plus cisplatin (GC) and concurrent chemo-radiotherapy are commonly used treatment options for resected GBC. Methods: GB-GECCOR is a multicentre, open-label randomized non-comparative phase II study in patients of Gallbladder cancer (GBC), with R0 or R1 resection within 3 months of randomization. Patients were randomized 1:1 to GC arm (Gem 1000 mg/m2 and Cisplatin 25mg/m2 on day 1 and 8, q 3 weeks) for 6 cycles or CAPE-RT arm {Capecitabine 1000mg/m2 BD on days 1-14, q 3 weeks for 2-4 cycles followed by chemoradiation (RT: 45 Gy over 25 fractions concurrent with capecitabine: 825mg/m2 twice) followed by 2-4 cycles of capecitabine for a total of 6 cycles}. The primary end point was 1-year disease-free survival (DFS). With 80% power to detect the difference between a 59% (minimum sufficient activity of the regimen) and a 77% (sufficient activity for future larger studies with the regimen) 1-year DFS rate assuming an attrition of 10%, a total of 90 patients were required for the study. Results: Between May 2019 and February 2022, 90 patients (45 in each arm), were included. Stage II and stage III GBC were seen in 50 (56%) and 40 patients (44%) respectively, with R0 resection observed in 86 patients (96%). Patient characteristics were well balanced between the 2 arms except for R1 resections which were greater in the CAPE-RT arm (p=0.041). With a median follow-up duration of 23 months, the 1-year DFS rate was 88.9% (95% CI: 79.5-98.3) in the GC group and 77.8% (95% CI: 65.4 – 90.2) in the CAPE-RT group, respectively. The most common AEs were grade 3/4 neutropenia in 6 patients (13.3%) in the GC group and grade 2/3 HFS in 14 patients (31.1.%) in the CAPE-RT group. The distant metastases were seen in 12 patients (26.6 %) in each arm and loco-regional metastases in 3 patients (6.6 %) in the GC arm. Conclusions: In this study of operated GBC, GC and CAPE-RT successfully achieved the minimum pre-specified DFS rates. Within the confines of a non-comparative randomised study, GC had narrowed the gap in survivals of stage III vs. stage II GBCs, which was not noted in the CAPE-RT arm. This study results give credence to the use of both regimens as reasonable standards of care till evaluation in larger phase 3 studies. Clinical trial information: CTRI/2019/05/019323 . [Table: see text]